Vitamin B5 Abstracts 2

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Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation
            (Evans et al., 2014) Download
High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines.


 

Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a "pro-inflammatory" state associated with atherosclerosis and autoimmunity.
            (Gominak, 2016) Download
STUDY OBJECTIVES:  Vitamin D blood levels of 60-80ng/ml promote normal sleep. The present study was undertaken to explore why this beneficial effect waned after 2years as arthritic pain increased. Pantothenic acid becomes coenzyme A, a cofactor necessary for cortisol and acetylcholine production. 1950s experiments suggested a connection between pantothenic acid deficiency, autoimmune arthritis and insomnia. The B vitamins have been shown to have an intestinal bacterial source and a food source, suggesting that the normal intestinal microbiome may have always been the primary source of B vitamins. Review of the scientific literature shows that pantothenic acid does not have a natural food source, it is supplied by the normal intestinal bacteria. In order to test the hypothesis that vitamin D replacement slowly induced a secondary pantothenic acid deficiency, B100 (100mg of all B vitamins except 100mcg of B12 and biotin and 400mcg of folate) was added to vitamin D supplementation. METHODS:  Vitamin D and B100 were recommended to over 1000 neurology patients. Sleep characteristics, pain levels, neurologic symptoms, and bowel complaints were recorded by the author at routine appointments. RESULTS:  Three months of vitamin D plus B100 resulted in improved sleep, reduced pain and unexpected resolution of bowel symptoms. These results suggest that the combination of vitamin D plus B100 creates an intestinal environment that favors the return of the four specific species, Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria that make up the normal human microbiome. HYPOTHESES:  1) Seasonal fluctuations in vitamin D levels have normally produced changes in the intestinal microbiome that promoted weight gain in winter. Years of vitamin D deficiency, however, results in a permanently altered intestinal environment that no longer favors the "healthy foursome". 2) Humans have always had a commensal relationship with their intestinal microbiome. We supplied them vitamin D, they supplied us B vitamins. 3) The four species that make up the normal microbiome are also commensal, each excretes at least one B vitamin that the other three need but cannot make. 4) Improved sleep and more cellular repairs eventually depletes body stores of pantothenic acid, causing reduced cortisol production, increased arthritic pain and widespread "pro-inflammatory" effects on the immune system. 5) Pantothenic acid deficiency also decreases available acetylcholine, the neurotransmitter used by the parasympathetic nervous system. Unopposed, increased sympathetic tone then produces hypertension, tachycardia, atrial arrhythmias and a "hyper-adrenergic" state known to predispose to heart disease and stroke.


 

Current medical aspects of pantethine.
            (Horváth and Vécsei, 2009) Download
Pantethine, the stable disulfide form of pantetheine, is the major precursor of coenzyme A, which plays a central role in the metabolism of lipids and carbohydrates. Coenzyme A is a cofactor in over 70 enzymatic pathways, including fatty acid oxidation, carbohydrate metabolism, pyruvate degradation, amino acid catabolism, haem synthesis, acetylcholine synthesis, phase II detoxification, acetylation, etc. Pantethine has beneficial effects in vascular disease, it able to decrease the hyperlipidaemia, moderate the platelet function and prevent the lipid-peroxidation. Moreover its neuro-endocrinological regulating role, its good influence on cataract and cystinosis are also proved. This molecule is a well-tolerated therapeutic agent; the frequency of its side-effect is very low and mild. Based on these preclinical and clinical data, it could be recommended using this compound as adjuvant therapy.

The long-term relationship between dietary pantothenic acid (vitamin B5) intake and C-reactive protein concentration in adults aged 40 years and older.
            (Jung et al., 2017) Download
BACKGROUND AND AIMS:  Low-grade inflammation, represented by minor C-reactive protein (CRP) elevation, has a critical role in the early stages of atherosclerosis, and pantothenic acid (PA) may have an antioxidant effect in inflammatory process. However, the long-term relationship between PA intake and CRP has not yet been studied. The objective of the present study was to evaluate the long-term relationship of PA intake to CRP concentration in healthy adults aged 40 years or older living in a rural area of South Korea. METHODS AND RESULTS:  A total of 908 subjects (349 men, 559 women) with repeated data on dietary PA intake and CRP concentration were included in the final analysis. To represent the long-term effect of PA intake, both PA intake at the baseline and average PA intake were used as the exposure, and CRP concentration at the third visit and its change from the baseline to the third visit were used as the outcome. After adjustment for potential confounders, a significant inverse relationship between PA intake and CRP concentration at the third visit was observed (P for trend = 0.001, β = -0.07 (P-value = 0.001) for PA  CONCLUSIONS:  In conclusion, dietary PA intake was inversely related to subsequent CRP concentration in both men and women aged 40 years or older in South Korea.


 

Dietary intake of pantothenic acid is associated with cerebral amyloid burden in patients with cognitive impairment.
            (Lee et al., 2018) Download
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-β peptide (Aβ) in diffuse and neuritic plaques. Previous research has suggested that certain vitamins may prevent this process. In the present study, we evaluated the relationship between vitamin intake and cerebral Aβ burden in patients with cognitive impairment. This study included 19 patients with subjective cognitive impairment and 30 patients with mild cognitive impairment. All patients underwent brain MRI and 18F-florbetaben positron emission tomography. The Food Frequency Questionnaire was used to evaluate dietary intake of the 15 vitamins. Intake of vitamin B6 (p = 0.027), vitamin K (p = 0.042), vitamin A (p = 0.063), riboflavin (p = 0.063), β-carotene (p = 0.081), pantothenic acid (p = 0.092), and niacin (p = 0.097) was higher in the Aβ-positive group than in the Aβ-negative group. Multivariate linear regression analysis revealed that pantothenic acid intake was an independent determinant of cerebral Aβ burden (β = 0.287, p = 0.029). No significant correlations were observed between cerebral Aβ burden and the intake of other vitamins. Our findings demonstrated that pantothenic acid intake may be associated with increased cerebral Aβ burden in patients with cognitive impairment. These results may offer insight into potential strategies for AD prevention.

Pantothenic acid as a weight-reducing agent: fasting without hunger, weakness and ketosis
            (Leung, 1995) Download
With the conventional method of fasting or aggressive dieting to reduce excess body fat, hunger, weakness, ketogenesis and ketosis are the sequential events that follow. It is not fully understood why, under conditions of negative calorie balance where complete energy release from storage fat is critical, ketosis should arise with a concomitant wastage of energy. Here, I wish to propose a theory that relates the formation of ketone bodies under such conditions to a deficiency in dietary pantothenic acid. Supplementation of this vitamin would facilitate complete catabolism of fatty acids and thus the formation of ketone bodies could be circumvented. As a result, a sufficient amount of energy would be released from storage fat to relieve dieters of the sensation of hunger and weakness which otherwise would be difficult to endure. Hence, using this method for weight reduction together with a careful observation of calorie intake, I have great success in treating overweight-to-obese patients to lose weight.


 

A stone that kills two birds: how pantothenic acid unveils the mysteries of acne vulgaris and obesity
            (Leung, 1997) Download
Acne vulgaris is the most common disease of the skin. Obesity is arguably the commonest of a clinical entities in the affluent society. The pathogenesis of these disorders is far from clear cut and they appear to have little in common. In the present paper it is hypothesized that the pathogenesis of both acne vulgaris and obesity is largely due to a relative deficiency of the same agent, pantothenic acid, a vitamin that is hitherto quite unknown to cause any deficiency syndromes in man. Furthermore, the evidence suggests that surprisingly large doses of pantothenic acid are required to overcome deficiency states as illustrated in the treatment of acne vulgaris and weight reduction.

Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington's Disease.
            (Patassini et al., 2019) Download
Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the HTT gene. HD usually manifests in mid-life with loss of GABAergic projection neurons from the striatum accompanied by progressive atrophy of the putamen followed by other brain regions, but linkages between the genetics and neurodegeneration are not understood. We measured metabolic perturbations in HD-human brain in a case-control study, identifying pervasive lowering of vitamin B5, the obligatory precursor of coenzyme A (CoA) that is essential for normal intermediary metabolism. Cerebral pantothenate deficiency is a newly-identified metabolic defect in human HD that could potentially: (i) impair neuronal CoA biosynthesis; (ii) stimulate polyol-pathway activity; (iii) impair glycolysis and tricarboxylic acid cycle activity; and (iv) modify brain-urea metabolism. Pantothenate deficiency could lead to neurodegeneration/dementia in HD that might be preventable by treatment with vitamin B5.

Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels.
            (Rébeillé et al., 2007) Download
Many efforts have been made in recent decades to understand how coenzymes, including vitamins, are synthesised in organisms. In the present review, we describe the most recent findings about the biological roles of five coenzymes: folate (vitamin B9), pantothenate (vitamin B5), cobalamin (vitamin B12), biotin (vitamin B8) and molybdenum cofactor (Moco). In the first part, we will emphasise their biological functions, including the specific roles found in some organisms. In the second part we will present some nutritional aspects and potential strategies to enhance the cofactor contents in organisms of interest.


Pantothenic acid in health and disease
            (Tahiliani and Beinlich, 1991) Download
In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)


 

Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial.
            (Vaxman et al., 1995) Download
This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars.

Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans.
            (Wall et al., 2012) Download
Reduced skeletal muscle free coenzyme A (CoASH) availability may decrease the contribution of fat oxidation to ATP production during high-intensity, submaximal exercise or, alternatively, limit pyruvate dehydrogenase complex (PDC) flux and thereby carbohydrate oxidation. Here we attempted to increase the muscle CoASH pool in humans, via pantothenic acid and cysteine feeding, in order to elucidate the role of CoASH availability on muscle fuel metabolism during exercise. On three occasions, eight healthy male volunteers (age 22.9 ± 1.4 yr, body mass index 24.2 ± 1.5 kg/m(2)) cycled at 75% maximal oxygen uptake (Vo(2max)) to exhaustion, followed by a 15-min work output performance test. Muscle biopsies were obtained at rest, and after 60 min and 91.3 ± 3.1 min of exercise (time to exhaustion on baseline visit) on each occasion. Two weeks following the first visit (baseline), 1 wk of oral supplementation with either 3 g/day of a placebo control (glucose polymer; CON) or 1.5 g/day each of d-pantothenic acid and l-cysteine (CP) was carried out prior to the second and third visits in a randomized, counterbalanced, double-blind manner, leaving a 3-wk gap in total between each visit. Resting muscle CoASH content was not altered by supplementation in any visit. Following 60 min of exercise, muscle CoASH content was reduced by 13% from rest in all three visits (P < 0.05), and similar changes in the respiratory exchange ratio, glycogenolysis (∼235 mmol/kg dry muscle), PCr degradation (∼57 mmol/kg dry muscle), and lactate (∼25 mmol/kg dry muscle) and acetylcarnitine (∼12 mmol(.)kg/dry muscle) accumulation was observed during exercise when comparing visits. Furthermore, no difference in work output was observed when comparing CON and CP. Acute feeding with pantothenic acid and cysteine does not alter muscle CoASH content and consequently does not impact on muscle fuel metabolism or performance during exercise in humans.

 


References

Evans, M., et al. (2014), ‘Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation’, Vasc Health Risk Manag, 10 89-100. PubMed: 24600231
Gominak, SC (2016), ‘Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity.’, Med Hypotheses, 94 103-7. PubMed: 27515213
Horváth, Z and L Vécsei (2009), ‘Current medical aspects of pantethine.’, Ideggyogy Sz, 62 (7-8), 220-29. PubMed: 19685700
Jung, S, MK Kim, and BY Choi (2017), ‘The long-term relationship between dietary pantothenic acid (vitamin B5) intake and C-reactive protein concentration in adults aged 40 years and older.’, Nutr Metab Cardiovasc Dis, 27 (9), 806-16. PubMed: 28739188
Lee, JH, et al. (2018), ‘Dietary intake of pantothenic acid is associated with cerebral amyloid burden in patients with cognitive impairment.’, Food Nutr Res, 62 PubMed: 30574044
Leung, L. H. (1995), ‘Pantothenic acid as a weight-reducing agent: fasting without hunger, weakness and ketosis’, Med Hypotheses, 44 (5), 403-5. PubMed: 8583972
Leung, LH (1997), ‘A stone that kills two birds: how pantothenic acid unveils the mysteries of acne vulgaris and obesity’, J Orthomolecular Medicine, 12 (2), 99-114. PubMed:
Patassini, S, et al. (2019), ‘Cerebral Vitamin B5 (D-Pantothenic Acid) Deficiency as a Potential Cause of Metabolic Perturbation and Neurodegeneration in Huntington’s Disease.’, Metabolites, 9 (6), PubMed: 31212603
Rébeillé, F, et al. (2007), ‘Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels.’, Nat Prod Rep, 24 (5), 949-62. PubMed: 17898891
Tahiliani, A. G. and C. J. Beinlich (1991), ‘Pantothenic acid in health and disease’, Vitam Horm, 46 165-228. PubMed: 1746161
Vaxman, F, et al. (1995), ‘Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial.’, Eur Surg Res, 27 (3), 158-66. PubMed: 7781653
Wall, BT, et al. (2012), ‘Acute pantothenic acid and cysteine supplementation does not affect muscle coenzyme A content, fuel selection, or exercise performance in healthy humans.’, J Appl Physiol (1985), 112 (2), 272-78. PubMed: 22052867