September 28, 2022

New review investigates the effect of Lactobacillus probiotic supplementation on blood pressure

According to a new review published last month in Complimentary Therapies in Medicine, researchers investigated the potential benefits of Lactobacillus supplementation on blood pressure. Previous clinical trials have shown inconsistent results. I have also recently shared research on the role of dysbiosis and probiotic supplementation on cardiovascular health and its impact on dyslipidemia.

This meta-analysis consisted of 18 randomized controlled trials published between 2012 and 2018. These studies included between 28 to 164 participants over a 3 to 24-week period. As a result, Lactobacillus supplementation significantly reduced systolic blood pressure and diastolic blood pressure compared to the placebo. This was consistent with the results from a previous meta-analysis. This reduction was modest, however, even small reductions in blood pressure can significantly reduce stroke, myocardial infarction, and mortality.

An additional subgroup analysis demonstrated patients with type 2 diabetes, Asian individuals, or patients with borderline hypertension had a more significant effect from the Lactobacillus supplementation. Also, the effect of Lactobacillus supplementation on blood pressure was more significant when it was delivered in a capsule form with the dose over 5 billion CFUs per day and longer than an 8-week duration. Furthermore, a subgroup analysis of Lactobacillus strains demonstrated that L. plantarum showed a slight decrease in blood pressure compared to other species.

Although, the underlying mechanisms of Lactobacillus on blood pressure has not been fully determined, animal studies have demonstrated Lactobacillus supplementation improves endothelial function preventing vascular inflammation and oxidative stress. In addition, L. plantarum can inhibit angiotension convert enzyme (ACE) activity as well as produce nitric oxide in the gastrointestinal tract.

Probiotics help encourage microbial diversity, especially if the probiotic supplement is of mixed species. In ecological terms, it is more stable to have diverse populations in any ecosystem. The same is true for the gastrointestinal microbiome. This study demonstrates that Lactobacillus supplementation over 5 billion CFUs in a capsule given for more than 8 weeks can decrease systolic and diastolic blood pressure in patients with type 2 diabetes, borderline hypertensive patients or Asian individuals. Previous meta-analyses showed similar findings with supplementing over 100 billion CFUs.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Liu J, Zhang D, et al. The Effect of Lactobacillus Consumption on Human Blood Pressure: a Systematic Review and Meta-Analysis of Randomized Controlled Trials. Complement Ther Med. 2020 Nov;54:102547. Epub 2020 Sep 2.

New study investigates Bacillus subtilis DE111 spore probiotic on lipid metabolism and endothelial function

Emerging research has demonstrated a role of dysbiosis in the gut microbiome and its impact on cardiovascular health.

According to a new study published this week in Beneficial Microbes, researchers investigated the cardiovascular effects of prebiotic and probiotic supplementation in healthy individuals.

This was a randomized, double-blind, placebo-controlled, four-arm intervention study in 88 healthy individuals between 18 to 65 years of age with a body mass index (BMI) between 20 and 34.9. Assessments included anthropometric measures, a lipid profile, blood pressure, pulse wave analysis, endothelial function, and a medical health history questionnaire. These were taken at baseline and at the end of the study. Everyone was instructed to maintain their regular exercise and dietary habits throughout the study. Each participant supplemented with Bifidobacterium animalis subsp. lactis strain BL04, with and without Escherichia coli-targeting bacteriophages, Bacillus subtilis strain DE111 or a maltodextrin-based placebo over a 4-week period.

As a result, there were no significant changes on the cardiovascular biomarkers in the individuals consuming B. lactis with or without bacteriophages. However, supplementation with B. subtilis demonstrated a significant reduction in total cholesterol as well as non-HDL cholesterol. This is most likely due to its effect that short chain fatty acids (SCFA) have on cholesterol metabolism. B. subtilis is known to stimulate the production of lactic acid by enhancing the growth of Lactobacillus spp. and SCFAs have been shown to inhibit the synthesis of hepatic cholesterol leading to a reduction in LDL and non-HDL cholesterol levels.  In addition, there was a trend showing improvements in LDL cholesterol and a modest increase in reactive hyperaemia index (RHI), a measure of endothelial function.

This study demonstrates that B. subtilis supplementation may be beneficial for improving risk factors associated with cardiovascular disease. Other nutrients to consider for dyslipidemia include delta and gamma tocotrienol isomers and fish oil supplementation.

It is also important to look deeper into the cardiovascular system. Health care providers have many tools to assess cardiovascular health and support the body’s physiology. It is essential to perform a thorough assessment for these patients. This may include looking at an advanced lipid profile, inflammatory markers, nutrient status, oxidative stress factors, heavy metals, and a fatty acid profile.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Trotter R.E, Vazquez A.R., et al. Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults. Beneficial Microbes, 2020; 1(7):621-630.


New study investigates the impact of dietary histamine intake in children with asthma

Asthma has become more prevalent over the past decade. Many patients have managed their asthma with medication and avoiding environmental triggers.

Previous research has demonstrated that diet can play a significant role in the development and symptoms in asthma. Histamine is an inflammatory mediator that has been associated with inflammation in asthma patients but its exact impact is not clear as the histamine content of food can vary significantly by a product’s maturity, time in storage, and processing. In addition, it is important to note that histamine secreting bacteria have been found at higher frequency in stool samples of asthmatic patients.

According to a new study published last week in Nutrients, researchers investigated the effect of controlling dietary histamine intake and its impact on respiratory symptoms in children with asthma.

This was a randomized crossover dietary intervention, two-period study including 18 children (10 boys and 8 girls) with mild to intermittent asthma. The research team investigated the impact of dietary histamine intake on asthma symptoms. Each child was randomized to either a high- or low-histamine diet for an 8 week-period. Following a 2-week washout period, each child was switched to the other diet for 8 weeks. Foods were ranked according to their histamine content and a dietitian advised parents to select foods specifically from the food list provided. Dietary intake was assessed from eight random 24 hour recalls with Food-Processor Nutrition Analysis Software. Asthma symptoms were assessed at baseline and after each diet period. Daily symptom scores as well as peak flow were recorded throughout the diet. The best out of 3 morning and evening Peak Expiratory Flow Rate (PEFR) were measured with flow meter and recorded on the food diary cards.

As a result, there was significantly higher air flow obstruction and an increase in disease severity following the high-histamine diet compared to lesser symptoms and more symptom-free days during a low histamine intake. This study demonstrates that diet can have a direct impact on asthma symptoms.

Since the pathophysiology of asthma is multifactorial as with many chronic diseases, there are several nutrients that should be considered to modulate the underlying dysfunction and immune response.

Previous research has demonstrated Lactobacillus supplementation improves asthma severity. Individuals receiving Lactobacillus containing probiotics all had lower asthma severity and higher ACT scores. In addition, the group that received both Lactobacillus strains demonstrated increased peak expiratory flow rates and lower IgE levels.

Low serum vitamin D levels have also been linked to an increased risk of asthma. There was a previous study from the journal Allergy which demonstrated that Vitamin D could help manage asthma attacks. Asthma patients with a Vitamin D deficiency were 25% more likely than other asthmatics to have had at least one flare-up in the recent past.

We know vitamin D has significant immunomodulatory effects and it has been shown to have an effect on asthma. Vitamin D has been shown to promote T regulatory cells and has been proposed as one of the causes of the increased prevalence of asthma.

Other nutrients to consider to relax the airways and provide anti-inflammatory properties include fish oil, magnesium, vitamin C, and curcumin.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Vassilopoulou E, Konstantinou G, et al. The Impact of Food Histamine Intake on Asthma Activity: A Pilot Study. Nutrients 5 November 2020, 12(11), 3402.


New study demonstrates the effects of long-term fish oil supplementation in patients with nonalcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has become an increasing epidemic. It is the most common cause of elevated liver enzymes and is associated with diabetes and obesity with advanced liver disease.

There are few guidelines for diagnostic and follow up methods and limited proven treatment options. Previous research of pharmacological agents to treat nonalcoholic fatty liver disease were performed with poor results.

According to a study just published this week in Nutrients, researchers investigated the effects of long-term fish oil supplementation in patients with nonalcoholic fatty liver disease (NAFLD).

This study was a randomized, double-blinded, placebo-controlled trial conducted between January 2018 and February 2020 including 24 patients over the age of 19 with ultrasound proven fatty liver disease. The patients were randomized to receive either fish oil supplementation (1,509 mg of DHA; 306 mg of EPA) or placebo (2,250 mg of oleic acid) over a six-month period. Assessments included circulating miR-122 expression, liver fibrosis (FibroScan®), RBC fatty acid profile, ALT, AST, alkaline phosphatase (ALP), GGT, fasting glucose, HA1c, and lipid profile were performed at baseline and after intervention.

As a result, there was a significant increase in the omega-3 index in the fish oil supplementation group. In addition, there was a significant decrease in ALP levels and liver fibrosis. ALP is commonly used as a marker of liver and bone pathology and is an independent risk factor for NAFLD. Also, increased levels of ALP have been shown in NAFLD patients in stages 1 and 2 of liver fibrosis. There was no difference in omega-3 index levels in the placebo group.

This study demonstrated that the fish oil supplementation was incorporated in the red blood cells after six months of supplementation and fish oil supplementation was effective in reducing liver fibrosis and ALP levels.

These individuals are in a chronic disease state and have increased demands then what could be obtained from the diet alone and therefore, dietary supplements should be considered to help prevent the progression as well as improve liver function. Other nutrients to consider include tocotrienols, phosphatidylcholine, fiber or resistant starch, n-acetylcysteine, and probiotics.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Cansancao K, Citelli M, et al. Impact of Long-Term Supplementation with Fish Oil

in Individuals with Non-Alcoholic Fatty Liver Disease: A Double Blind Randomized Placebo Controlled Clinical Trial. Nutrients 2 November 2020, 12(11), 3372.

New study demonstrates low magnesium levels associated with increased dementia risk

Dementia affects one’s ability to function socially, personally, and professionally. It is important to recognize that dementia begins long before symptoms start just like many other conditions. There is evidence that prevention strategies may reduce the risk by as much as 50%.

According to a new study published last week in Nutrients, researchers investigated the role of magnesium levels in cognitive decline and dementia over a 27-year period. Magnesium is often cited as the nutrient most deficit and has been shown to have beneficial effects in multiple chronic conditions such as diabetes, stroke, and cardiovascular disease. Since these conditions increase the risk of cognitive decline and dementia, magnesium may have a protective role.

This study was a large, community-based cohort including 12,040 participants that did not have dementia in the Atherosclerosis Risk in Communities (ARIC) study. Serum magnesium levels were measured in 1990 through 1992. Dementia status was determined by cognitive examinations performed in 2011–2013, 2016–2017, 2018–2019 as well as from interviews, dementia related hospitalization events, and death. Each patient’s cognitive functioning was assessed up to 5 times between 1990–1992 and 2018–2019.

The research team identified 2,519 cases of dementia over an average follow-up period of 24 years. As a results, the lowest quintile of serum magnesium was associated with a 24% higher rate of incident dementia compared to those in the highest quintile of magnesium even after adjusting for demographics, lifestyle, cardiovascular risk factors, APOE4 carrier status, and other micronutrients. No relationship was found between serum magnesium and cognitive decline.

In summary, low serum magnesium is associated with increased risk of dementia but did not appear to impact rates of cognitive decline but It is important to note that cognitive performance at visit 2 was poorer among participants with lower serum magnesium compared to those with higher magnesium.

Magnesium targets numerous pathways in the pathology of dementia. Magnesium is able to inhibit excitotoxicity of NMDA receptors and inhibit excessive beta-amyloid production. An ideal form of magnesium for these individuals would be magnesium glycinate and magnesium l-threonate. Mangesium glycinate is a great bioavailable form of magnesium that can be used to increase intracellular levels of magnesium and magnesium l-threonate is a novel form of magnesium that crosses the blood brain barrier and increases brain magnesium levels. There have been a few human studies demonstrating its effects in Alzheimer’s’ disease and mild cognitive impairment.

Other brain supportive nutrients to consider are GPC, CDP-choline, gingko biloba, phosphatidylserine, curcumin, folate, cobalamin, and fish oil.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Alam A, Lutsey P, et al. Low Serum Magnesium is Associated with Incident Dementia in the ARIC-NCS Cohort. Nutrients 9 October 2020, 12(10), 3074.


Recent study demonstrates lower vitamin C intake and status is associated with decreased lean body mass

Aging is associated with chronic low-grade inflammation, sarcopenia and functional decline. The loss of muscle mass between the ages of 40 and 80 is approximately between 30% and 60% and is associated with disability, illness, and death.

Vitamin C has several functions that may prevent age-related skeletal muscle loss. Vitamin C is involved in the synthesis of carnitine and collagen, it can reduce oxidative damage to muscle, and reduce inflammation in the circulation. Although the mechanisms of vitamin C and muscle physiology is known, human clinical studies are lacking.

According to a recent study published in The Journal of Nutrition, researchers investigated cross-sectional associations of dietary and plasma levels of vitamin C and its relationship on muscle mass.

The research team analyzed data from over13,000 individuals between the ages of forty-two and eighty-two. Skeletal muscle mass was estimated using bioelectrical impedance analysis and expressed as a percentage of fat-free mass or standardized by BMI. Dietary vitamin C intakes were assessed using a 7-day food diary and plasma vitamin C levels were measured. This method has been found to be more accurate than food frequency questionnaires (FFQs). Each individual recorded all food and drink including portion sizes. The Data into Nutrients for Epidemiologic Research (DINER) software was used to document dietary information and convert it into nutrient quantities.

This is the first study to investigate the relationship of dietary and vitamin C levels and the loss of skeletal muscle mass as a sarcopenic risk factor in individuals of middle and older age. As a result, there were significant positive associations between dietary vitamin C intake and measures of fat-free mass using multivariable regression models. Although the associations were significant in both men and women, the results were greater in women. Dietary vitamin C intake was reinforced and validated with plasma vitamin C levels.

These findings demonstrate the importance of obtaining adequate dietary or supplemental vitamin C intake in reducing age-related muscle loss. Interestingly, an animal study demonstrated a reversal of muscle atrophy with the reintroduction of vitamin C into the diet. Other nutrients to consider include vitamin D, magnesium, collagen, BCAAs, tocotrienols, and probiotics.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Lewis L, Hayhoe R, et al. Lower Dietary and Circulating Vitamin C in Middle- and Older-Aged Men and Women Are Associated with Lower Estimated Skeletal Muscle Mass. J Nutr. 2020 Aug 27;nxaa221. doi: 10.1093/jn/nxaa221.




New review investigates the effects of carnitine supplementation on metabolic syndrome

Metabolic syndrome and insulin resistance are a significant health care problem in the United States. Type 2 diabetes affects more than 300 million people.

Insulin resistance is preventable and reversible through lifestyle changes, proper nutrition, supplements, exercise, and stress management. Weight loss and exercise are the best treatments for restoring the body’s ability to respond to insulin.

A previous review demonstrated that L-carnitine supplementation reduced body weight, body mass index, and fat mass.

According to a new review published last week in Nutrients, researchers investigated the effects of carnitine supplementation on specific biomarkers of metabolic syndrome.

This review consisted of 9 randomized placebo controlled trials including 508 patients. Clinical trials were included if they had at least one of the following assessments: waist circumference, blood pressure, fasting glucose levels, triglycerides, or HDL levels. The studies ranged in size from 18 to 81 individuals over a duration between 8 to 24 weeks. The most common study duration was 12 weeks and the average age of the patient was forty-one. Six of the studies used L-carnitine as the only treatment, one used L-carnitine along with calorie restriction, and two used a L-carnitine combined with calorie restriction and exercise. The daily dose of L-carnitine used ranged from 750 mg to 3 grams day with 2 grams being the most common.

Two of the studies demonstrated changes in waist circumference, two in blood pressure, five in fasting glucose levels, six in triglycerides, and five in HDL levels. As a result, L-carnitine supplementation significantly reduced waist circumference and systolic blood pressure. In addition, the research team found that L-carnitine supplementation at a dose of more than 1 gram per day significantly reduced fasting glucose levels and triglycerides. Also, L-carnitine supplementation increased HDL levels.

In summary, L-carnitine supplementation is correlated with a significant reduction of waist circumference and blood pressure. A dosage between 1 to 3 grams per day should be considered to improve the biomarkers of metabolic syndrome. Other nutrients to consider include inositol, tocotrienols, lipoic acid, fish oil, magnesium, and glycine.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Choi M, Park S, and Lee M. L-Carnitine’s Effect on the Biomarkers of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients 12 September 2020, 12(9), 2795.

New review investigates the effects of taurine supplementation on obesity, blood pressure, and lipid profile

Taurine is a sulfur containing amino acid that is found in high concentration in the heart and white blood cells. It plays an important role in regulating glucose, lipid metabolism, and blood pressure but results in human clinical studies have been inconsistent.

According to a review published three weeks ago in the European Journal of Pharmacology, researchers investigated the effects of taurine supplementation on obesity, blood pressure, and lipid profile. Taurine is found in animal food sources such as turkey, chicken, and shellfish and dietary intake has been inversely correlated to mortality rates associated with cardiovascular disease. The average daily intake of taurine is between 40 mg to 400 mg in non-vegetarians, so it makes sense that supplementation can provide a therapeutic effect.

This review included 12 randomized controlled trials including 391 individuals who consumed either taurine supplementation or placebo on cardiovascular biomarkers including blood pressure and lipid profile in patients with obesity as well as anthropometric measurements. Most of these studies were in patient populations with liver or metabolic dysfunction including type II diabetes, hepatitis, and non-alcoholic fatty liver disease. The taurine supplementation doses ranged between 500 mg up to 6 grams per day over a duration between a 2-week and 6-month period. The two most common doses used were 1.5 grams or 6 grams per day.

As a result, there was a significant effect of taurine supplementation on systolic blood pressure and diastolic blood pressure, total cholesterol, and triglycerides. There was no effect of taurine supplementation on fasting blood glucose levels, LDL cholesterol, body mass index, or body weight.

Taurine’s effects on hypertension are due to its role of enhancing endothelial function and reduction of oxidative stress. Some of the taurine’s mechanisms on dyslipidemia include promoting cholesterol excretion, impeding bile acid absorption, and suppression of HMG-CoA reductase. The beneficial effects of taurine on obesity are attributed to its role in reducing inflammation of adipocytes and increasing adiponectin levels, which are associated with improved insulin sensitivity and anti-inflammatory actions.

These results demonstrate that taurine supplementation can lower blood pressure and improve dyslipidemia by reducing total cholesterol and triglyceride levels. Other nutrients to consider include delta and gamma tocotrienols, fish oil, and magnesium.

 By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Guan L, Miao P. The effects of taurine supplementation on obesity, blood pressure and lipid profile: A meta-analysis of randomized controlled trials. Eur J Pharmacol. 2020 Aug 29;885:173533.

New study investigates the effect of high-dose vitamin D supplementation in patients with diabetic neuropathy

Type II diabetes affects more than 30 million individuals and the youth account for 20% to 50% of new onset diabetes cases.

Previous research has demonstrated low levels of vitamin D are associated with an increased risk of type II diabetes. Vitamin D has been shown to play a role in reducing inflammation and inhibiting β-cell destruction. 

According to a new study two weeks ago in Nutrients, researchers investigated the effect of high-dose vitamin D supplementation on microcirculation, inflammatory markers, and peripheral neuropathy symptoms in patients with type II diabetes.

This study included 67 patients with type II diabetes and peripheral neuropathy. The research team investigated the effect of different doses of vitamin D supplementation on microcirculation, neuropathy symptoms, and inflammatory markers in patients with type II diabetes. Each patient was given either 5,000 IU or 40,000 IU once a week over a 24-week period. Neuropathy assessment included neuropathic symptomatic score (NSS), neuropathic disability score (NDS), and visual analogue scale (VAS). Cutaneous microcirculation (MC) was assessed by laser Doppler flowmetry (LDF). Laboratory assessment included total cholesterol, C-reactive protein, HA1c, vitamin D 25-OH, parathyroid hormone (PTH), IL-1β, IL-6, IL-10, and TNFα. These were assessed at baseline and after treatment.

A vitamin D deficiency or insufficiency was identified in 78% of the patients. As a result, vitamin D supplementation at 40,000 IU once a week demonstrated a significant decrease in neuropathy severity as well as an improvement of cutaneous microcirculation. In addition, there was a reduction in IL-6 levels and an increase in IL-10 levels. No changes were shown in patients that received vitamin D supplementation at 5,000 IU once a week.

This study demonstrated that high-dose vitamin D supplementation can reduce inflammation as well as improve microcirculation and neuropathy symptoms in patients with type II diabetes.

It is important to take vitamin K along with vitamin D to prevent against arterial calcification. It is also essential to maintain adequate levels of all the fat soluble vitamins as more and more research demonstrates their intricate interrelationships with other nutrients.

All chronic conditions are multifactorial and vitamin D is many times part of the picture. Other nutrients that can support neuropathy symptoms include benfotiamine, folate, cobalamin, pyridoxal-5-phosphate, acetyl-l-carnitine, and lipoic acid.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Karonova T, Stepanova A, et al. High-Dose Vitamin D Supplementation Improves

Microcirculation and Reduces Inflammation in Diabetic Neuropathy Patients. Nutrients. 20 August 2020, 12(9), 2518.



New study demonstrates success of low FODMAP diet in IBS for long term treatment

Irritable bowel syndrome (IBS) can be debilitating causing cramping, abdominal pain, bloating, gas, diarrhea and constipation. IBS can affect and one’s work, sleep and relationships.

Most treatments for IBS consist of medications that are often ineffective and can have numerous side effects. A low-FODMAP (Fermentable Oligo-Di-Monosaccharides and Polyols) diet is not a new treatment. Most functional medicine practitioners often incorporate a low FODMAP diet for patients with IBS, however, many of the dietary recommendations have not been backed by clinical trials.

According to a new study published last week in Nutrients, researchers investigated the short and long term efficacy, nutritional adequacy, and long term acceptance of a low FODMAP in patients with IBS. The patients’ compliance and ability to identify food triggers was also evaluated.

This study included 41 patients with IBS were given low-FODMAP diet and after two months started to reintroduce foods and then were treated with an Adapted low-FODMAP diet for a 6 to 24 month follow up. At each follow up visit questionnaires and Biolectrical Impedance Vector Analysis (BIVA) were performed. As a result, the low-FODMAP diet was effective in controlling gastrointestinal symptoms both short and long term as well as improving quality of life, anxiety, and depression. In addition, the low-FODMAP diet improved the quality of life without affecting nutritional adequacy. It was also noted that the perception of trigger foods was significantly different between the baseline and after two months. As a result, the research team demonstrated that even if there were some problems of acceptability and adherence reported, an low-FODMAP is nutritionally adequate and efficacious in improving IBS symptoms long term.

Diet is the most effective means to returning balance within the gastrointestinal system. Some patients may need a combination of botanicals, enzymes, and probiotics to optimize the gastrointestinal environment. Certain diagnostic tests may also be beneficial, including stool testing as well as food antibody testing.

The gastrointestinal tract is considered to be the body’s ‘second brain,’ it is made up of a self-contained, complex network of neurons, neurotransmitters, and proteins embedded in the lining of the GI system. It is responsible for all aspects of the digestive process, from the esophagus to the stomach and small and large intestines and may be responsible for IBS symptoms.

There are other nutrients that can support patient with IBS. For example. Perilla frutescens is an herb native to Eastern Asia that demonstrates antispasmodic, prokinetic, and anti-inflammtory effects, which help normalize and promote health bowel function and provide relief from GI symptoms. In addition, there are some specific researched strains such as Saccharomyces cerevisiae CNCM I-3856 that have been shown to reduce digestive discomfort and abdominal pain in individuals with IBS.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Bellini M, Tonarell S, et al. A Low-FODMAP Diet for Irritable Bowel Syndrome: Some Answers to the Doubts from a Long-Term Follow-Up. Nutrients, 7 August 2020, 12(8), 2360.