(r)Alpha Lipoic Acid Is a Safe, Effective Pharmacologic Therapy of Chronic Orthostatic Hypotension Associated with Low Sympathetic Tone (2024)

  • Journal List
  • Int J Angiol
  • v.28(3); 2019 Sep
  • PMC6754261

As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health.
Learn more: PMC Disclaimer | PMC Copyright Notice

(r)Alpha Lipoic Acid Is a Safe, Effective Pharmacologic Therapy of Chronic Orthostatic Hypotension Associated with Low Sympathetic Tone (1)

Link to Publisher's site

Int J Angiol. 2019 Sep; 28(3): 188–193.

Published online 2019 Feb 22. doi:10.1055/s-0038-1676957

PMCID: PMC6754261

PMID: 31548784

Gary L. Murray, MD, FICA1 and Joseph Colombo, PhD2,3

Author information Copyright and License information PMC Disclaimer

Abstract

Chronic orthostatic hypotension (OH), affecting 10 to 30% of the elderly, is associated with falls, and increased morbidity and mortality. Current pharmacologic therapy can cause or worsen hypertension and fluid retention. (r)α lipoic acid (ALA), a powerful natural antioxidant, avoids those complications and may assist management of chronic neurogenic orthostatic hypotension (NOH). The purpose of this study is to demonstrate improvement in the symptoms of orthostatic dysfunction with r-ALA, including improved sympathetic (S) and blood pressure (BP) responses to head-up postural change (standing).

A cohort of 109 patients with low S tone upon standing was detected using the ANX −3.0, Autonomic Monitor, ANSAR Medical Technologies, Inc., Philadelphia, PA. From the cohort, 29 patients demonstrated NOH (change in (∆) standing BP ≥ −20/–10 mm Hg); 60 patients demonstrated orthostatic intolerance (OI, ∆ standing systolic BP between –6 and –19 mm Hg). These 89 were given ALA orally: either 590 to 788 mg (r)ALA or 867 to 1,500 mg of the less expensive 50 to 50% mixture (r)ALA and inactive (s)ALA. Changes in their S and parasympathetic (P) tone, and BPs, were compared with 20 control patients during mean follow-up of 2.28 years.

Nineteen of 29 (66%) NOH patients responded with a ∆ standing BP from –28/–6 mm Hg to 0/+2 mm Hg. Forty of 60 (67%) of patients with OI responded with a ∆ standing BP of –9/+1 mm Hg to +6/+2 mm Hg. Although all patients treated with ALA increased S tone, the ∆ BP depended upon the pretreatment of S tone. Those with the lowest S tone responded the least well. The only treatment side effects were nausea, intolerable in only 5%. Nausea improved with routine gastrointestinal medications. Glucose levels improved in the 28% of patients who were diabetic. Also, resting hypertension improved. Control patients had no ∆ BP and no increase in S tone.

(r)ALA improves S-, and BP, responses to head-up postural change, and thereby NOH/OI, in a majority of patients without causing harmful side effects.

Keywords: α-lipoic acid, orthostatic hypotension, autonomic nervous system, parasympathetic nervous system, sympathetic nervous system

Chronic orthostatic hypotension (OH, defined as fall of systolic blood pressure [BP] or diastolic BP ≥ 20/10 mm Hg within 3 minutes of standing still) is prevalent at any age, but mostly in the elderly1in whom neurogenic orthostatic hypotension (NOH [such as low sympathetic (S) tone with head-up postural change (i.e., standing)]) is by far more common than venostasis or iatrogenic causes, with OH prevalence rates up to 30%.2OH is a common cause of lightheadedness in elderly or chronic disease patients and is one of the earliest, and arguably the most debilitating, symptom of autonomic dysfunction.34

OH is associated with increased mortality in the elderly: hazard ratios of systolic BP OH: 1.69 to 2.04; diastolic BP OH: 2.2.5OH in diabetics can be an early manifestation of cardiac autonomic neuropathy, and possibly in nondiabetics and the elderly. Cardiac autonomic neuropathy increases mortality by 25 to 50% within 10 years,6and heart failure death or hospitalization is also high (hazard ratio 1.85).7Oxidative stress, regardless of the source (sugar acidosis, low antioxidant levels, psychosocial stress, lack of exercise, smoking, pollution, etc.), causes autonomic injury that precedes diabetic autonomic neuropathy. Autonomic injury affects all systems of the body. Oxidative and nitrosative stress damages the more sensitive tissues, including peripheral and central nerves, endothelial cells, immune cells, the microvasculature, and glomerular filtration structures. Therapies known to reduce oxidative stress are therefore recommended. α-lipoic acid (ALA), through its multiple antioxidant properties, has long been found to slow or stay the progression of autonomic injury.89

The autonomic nervous system plays a critical role in BP regulation.10Since (r) ALA has been used in treating diabetic cardiac autonomic neuropathy, including orthostatic dysfunction and hypertension,11121314we postulated it might improve NOH as well as orthostatic intolerance (OI) in nondiabetics, without causing or worsening hypertension or volume overload; as do most frequently used pharmacologic agents.15

As human longevity increases worldwide, OH will become increasingly problematic. Presently, most types of OH are treated similarly. Medications with hypotensive side effects are reduced or discontinued, compression hose for lower extremity edema, and occasional abdominal binders to increase venous return, fludrocortisone, increased oral fluid and salt intake to increase plasma volume, midodrine for vasoconstriction, and most recently droxidopa to increase norepinephrine levels.16Other medications are uncommonly used.1718However, many of these measures can cause or exacerbate pre-existing hypertension, or worsen congestive heart failure. Clearly, much more efficacious treatment is needed.

ALA is a naturally occurring substance, a powerful thiol antioxidant that restores and recycles vitamins A, C, E, and glutathione, enhancing their efficacy. ALA also improves hyperglycemia, endothelial dysfunction, nitric oxide levels; reduces nuclear factor kappa B activity, is essential for the function of certain oxidative enzymatic activities; and has been mainly used to treat diabetic dysautonomia.19It also suppresses neurologic intracellular accumulation of α-synuclein, the major cause of NOH in many neurologic diseases.2021It exists as two enantiomers, with (r)ALA much more active than (s)ALA, and does not require a prescription. ALA treatment seems safe and effective (without hypertensive side effects or volume overload) for NOH or OI patients, even in nondiabetics. The purpose of this study is to demonstrate improvement in the symptoms of orthostatic dysfunction with r-ALA, including improved S and BP responses to head-up postural change (standing).

Methods

Using the ANX-3.0 Autonomic Monitor (ANSAR Medical Technologies, Inc., Philadelphia, PA), sympathetic- (S) and parasympathetic (P)-activity were computed simultaneously and independently based on concurrent, continuous, time frequency analysis of respiratory activity, and heart rate variability.222324252627P activity measured as the respiratory frequency area (RFa) is defined as the spectral power within a 0.10 Hz-wide window centered on the fundamental respiratory frequency in the heart rate variability spectrum. Fundamental respiratory frequency is identified as the peak spectral mode from time-frequency analysis of respiratory activity. RFa is a measure of vagal outflow as it affects the heart. S activity (low frequency area [LFa]) is defined as the remaining spectral power in the low-frequency window (0.04–0.15 Hz) of the heart rate variability spectrum, after computation of RFa.

P- and S activity was recorded from a standard autonomic test, including (1) 5 minutes rest (seated), (2) 1 minute of breathing at 6 breaths/minute, (3) a series of 5 Valsalva maneuvers, including a 15 second Valsalva maneuver, and (4) a quick stand to 5 minutes of quiet standing. The average ratio of resting S to P activity (sympathovagal balance) reported was the average of the ratios recorded during the sampling period, not the ratio of the averages.28

A cohort of 109 patients with low S tone upon standing was detected using the ANX -3.0, Autonomic Monitor, ANSAR Medical Technologies, Inc., Philadelphia, PA. From the cohort, 29 patients demonstrated NOH (change in (∆) standing BP ≥ −20/–10 mm Hg) and 60 patients demonstrated orthostatic intolerance (OI, ∆ standing systolic BP between –6 and –19 mm Hg). These 89 were given ALA orally: either 590 to 788 mg (r)ALA or 867 to 1,500 mg of the less expensive 50 to 50% mixture (r)ALA and inactive (s)ALA. Changes in their S- and P tone, and BPs, were compared with 20 control patients during mean follow-up of 2.28 years.

All 109 study patients had low S sitting or standing. The only change in patients' therapy was the addition of (r)ALA or ALA (a racemic mixture of (r)- and (s)ALA). Syncopal responders had no recurrence of syncope, otherwise response was defined as ∆ standing systolic BP < –6 mm Hg.

This study was approved by our Institutional Review Board, and all patients signed informed consent.

Statistical Analyses

Continuous data were assessed for normality with normally distributed data analyzed using Studentt-tests and non-normally distributed data using a Mann–Whitney U test. Dichotomous data were analyzed using the chi-square test or Fisher's exact test. Ap-value of ≤ 0.05 was considered significant. Studentt-tests were performed as two-tailed with equal variance. Significance values were determined on the null hypothesis that the pre- and post-treatment values are equal.

Results

Patient demographicsare listed inTable 1. In the OH Group (n = 29),1there were no females in the 10 nonresponders;2there were more diabetics;380% were prescribed midodrine, fludrocortisone, or desmopressin; and420% were on beta-blockers. There were fewer patients with hypertension or congestive heart failure, but more with syncope. In the OI group (n = 60), there were fewer congestive heart failure patients, but more with syncope, fatigue, and headache.

Table 1

Patient demographics

OH (n = 29)pOI (n = 60)pControl (n = 20)p
R–(10)R + (19)R–(20)R + (40)
Age (mean, yrs)72 ± 13.870 ± 9.6ns69 ± 7.564 ± 9.5ns66 ± 9.0ns
Gender (M%)9680.0106058ns40ns
Symptoms (% of population)
Fatigue4037ns65300.03030n/a
Dizziness70470.0105537.5ns30n/a
Syncope40260.0495022.50.04910n/a
Headache0ns1000.016310n/a
Medications (% of population)
Midodrine500<0.00150ns5n/a
Fludrocortisone300<0.00100ns0n/a
Desmopressin2000.00100ns0n/a
(r)ALA (%)8068ns8572.5ns0n/a
(r)ALA mean dose (mg)610 ± 510754 ± 5700.080788 ± 510590 ± 5000.0300n/a
ALA2032ns1527.50.0600n/a
ALA mean dose (mg)1500 ± 760867 ± 4400.0351000 ± 460993 ± 450ns0n/a
Follow-up (mean yrs)2.28 ± 1.61.74 ± 2.0ns1.94 ± 1.51.29 ± 1.2ns2.16 ± 1.7ns

Open in a separate window

Abbreviations: ALA, α lipoic acid; n/a, not applicable;n, number; ns, not significant; OH, orthostatic hypotension; OI, orthostatic intolerance;R +, responders;R–, nonresponders; yrs, years.

Patient autonomics and BPsare listed inTables 2and​and3.3. In the OH group, pre-and post-treatment ∆ standing BP was –32/–9 mm Hg versus –29/–11 mm Hg in nonresponders, and –28/–6 mm Hg versus 0/+2 mm Hg in responders. In the OI group, pre- and post-treatment ∆ standing BP was −13/−19 mm Hg versus −12/+2 mm Hg in nonresponders, and −9/+1 mm Hg versus +6/+2 mm Hg in responders. Responders had higher S tone (Table 3). Regardless of the ∆ standing BP, (r)ALA reduced sitting BP in most patients. In the controls, there was no significant difference in ∆ standing BP (from a baseline of −13/−1 to a follow-up of −13/+3), and there was a decrease in S activity with follow-up.

Table 2

Autonomic and blood pressure measures

OHOIControls (n = 20)
R+ (n = 19)R– (n = 9)R+ (n = 40)R– (n = 20)InitialFinalp
PrePostpPrePostpPrePostpPrePostp
Rest (sitting)
BP, systolic (mm Hg)1451260.0023136136ns1301240.00611381300.0167140138ns
BP, diastolic (mm Hg)73660.00397776ns7069ns7169ns7672ns
LFa (bpm2)0.781.200.01720.200.25ns0.770.72ns0.410.560.03621.140.900.0301
RFa (bpm2)0.971.830.01990.340.27ns0.710.67ns0.490.59ns0.510.700.0517
SB (unitless)1.351.59ns1.251.12ns1.551.61ns1.431.37ns2.282.20ns
Valsalva
SB (unitless)9.598.90ns12.513.6ns9.0911.1ns6.1020.00.065214.012.6ns
Stand
BP, systolic (mm Hg)1171260.0210104107ns121130ns1251180.0433127125ns
BP, diastolic (mm Hg)6768ns6865ns7173ns52710.03387575ns
LFa (bpm2)0.530.880.03610.110.290.03620.920.98ns0.480.62ns1.690.550.0221
RFa (bpm2)0.691.030.03000.140.11ns0.470.47ns0.400.55ns1.690.550.0056
SB (unitless)2.241.690.00831.702.460.06542.944.200.02712.371.99ns4.081.910.0164
∆BP, systolic (mm Hg)–2800.0129–32–29ns–96<0.001–13–12ns–13–13ns
∆BP, diastolic (mm Hg)–620.0456–9–11ns12ns–1920.0068–13ns

Open in a separate window

Abbreviations: ∆, change; BP, blood pressure (mm Hg); LFa, low frequency area (beats/min2);n, number; ns, not significant; OH, orthostatic hypotension;R +, (R)α lipoic acid responders;R–, (R)α lipoic acid nonresponders; RFa, respiratory frequency area (beats/min2); SB, sympathovagal balance.

Table 3

Sympathetic activity as measured by LFa (bpm2)

Sympathetic activity (LFa, bpm2)RR+
OHOIpOHOIp
Pre-Rx
 Sit0.200.410.02300.780.77na
 Stand0.110.480.01070.530.920.0220
Post-Rx
 Sit0.250.560.02581.200.920.0345
 Stand0.290.120.02530.880.98na

Open in a separate window

Abbreviations: ∆, change; LFa, low frequency area (beats/min2); OH, orthostatic hypotension; OI, orthostatic intolerance;R +, (R)α lipoic acid responders;R–, (R)α lipoic acid nonresponders; Rx, treatment with (r)ALA.

Discussion

NOH is caused by failure of the baroreceptor reflex and/or too low S tone, usually as a result of neurologic intracellular α-synuclein production and aggregation.20ALA suppresses this as an antioxidant, improving the baroreceptor reflex and S tone, in contrast to the commonly used medications, so it should affect healing of the disorder, rather than simply treating its symptoms. Furthermore, it uniquely reduces resting hypertension and endothelial dysfunction.2930313233

Although only 28% of the patients were diabetic (Table 1), 59 of 89 (66% of all) patients responded to ALA. Sixteen of the 25 diabetics (64%) responded and 43 of 64 (67%) nondiabetics (p = ns), suggesting that ALA may be equally effective for all patients with orthostatic dysfunction. Nineteen of 29 (66%) NOH and 40 of 60 (67%) OI patients responded to ALA (p = ns), furthering the above suggestion.

(r)ALA raised LFa (S activity) in all patients except in OI nonresponders (Table 2). Treatment ∆ BP was related to pretreatment S activity. Those with the lowest sitting to standing change in S activity were the nonresponders (Table 3); perhaps droxidopa would be useful in these patients.

Responders had both a decrease in mean sitting BP (145/72–125/68 mm Hg, pre- to post-(r)ALA treatment, mean dose 643 mg/d or ALA 949 mg/d), and an increase in mean standing BP (120/70–129/71 mm Hg, pre- to post-treatment). This ∆ sitting BP indicates an improvement in resting hypertension and the ∆ standing BP indicates an improvement in orthostatic dysfunction. OI nonresponders demonstrated a +19 mm Hg (increase) in standing diastolic BP, which is vital in preserving coronary perfusion (Tables 1,​,2).2). In patients with coronary artery disease, a J-curve relationship has been reported between BP and major adverse cardiac events.33Given this J-curve of coronary flow and since major adverse cardiac events increase at diastolic BPs < 60 to 70 mm Hg,33the increase in diastolic BP in the OI nonresponder group could have been considered a positive OI response, but we defined a positive response as a standing decrease in only systolic BP less than −6 mm Hg, and the absence of syncope. Even though the OI nonresponders' standing systolic BP fell 6 mm Hg or more (an average fall of 12 mm Hg,Table 2), their diastolic BPs increased significantly (from a fall of 19 mm Hg to an increase of 2 mm Hg;p = 0.0068,Table 2). This improved outcome would raise the positive response rate to (r)ALA to 88% had we considered the J-curve of coronary perfusion,

Although previous human studies of the effect of ALA upon high BP have been mixed,34it can reduce high BP, increase baroreceptor reflex afferent limb sensitivity, improve endothelial dysfunction, increase nitric oxide, and improve diabetic dysautonomia. In our 19 OH responders, mean ∆BP to standing from pre- to post-treatment was –28/–6 mm Hg (sitting to standing, pretreatment) to 0/+2 mm Hg (sitting to standing, post-treatment). To date, we know of no other pharmacologic treatment that both decreases resting hypertension and OH. Such treatment has the potential to reduce substantially major cardiovascular events such as stroke, congestive heart failure, myocardial infarction, and cardiovascular death (major adverse cardiac events), as well as therapeutic costs and side effects. Nausea, rare flushing, and biotin depletion are the only known side effects of (r)ALA or ALA, and are harmless and easily treatable.

In the 20 control patients, S activity decreased, although ∆ BP did not, possibly because their initial S activity was the highest of all groups. Regardless, the decrease in S activity may be the prelude to further decreases in BP, if therapy is not prescribed. Since S activity controls BP and BP changes with stand (and other activities), the persistent decrease in S activity with stand indicates that there is a continued drive to further decrease BP upon standing, exacerbating orthostatic dysfunction and the associated morbidity and mortality risks. Because these untreated patients' S activity might continue to fall, perhaps they should be started on (r)ALA or ALA.

Limitations

A larger, longer study that also determines if ALA reduces major adverse cardiac events in NOH, and whether progression of these conditions is slowed, is needed. Additionally, if there is a partial response to therapy, what should be done next? Certainly, adjusting other hypotensive medications without absolute indications would seem obvious. Finally, our definition of OI was arbitrary.

Conclusion

(r)ALA or ALA appears to safely improve NOH and OI by increasing standing S activity, as measured by LFa, and thereby standing BP responses to stand.

Funding Statement

FundingNo funding was provided.

Footnotes

Conflict of Interest Dr. Murray has no disclosures. Dr. Colombo is Vice-President of ANSAR Medical Technologies, Inc., Philadelphia, PA.

References

1. Bradley J G, Davis K A. Orthostatic hypotension. Am Fam Physician. 2003;68(12):2393–2398. [PubMed] [Google Scholar]

2. Metzler M, Duerr S, Granata R, Krismer F, Robertson D, Wenning G K. Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management. J Neurol. 2013;260(09):2212–2219. [PMC free article] [PubMed] [Google Scholar]

3. Vinik A I, Maser R E, Nakave A A.Diabetic cardiovascular autonomic nerve dysfunctionUS Endocrine Disease. 2007; Dec: 2–9

4. Vinik A I, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115(03):387–397. [PubMed] [Google Scholar]

5. Luukinen H, Koski K, Laippala P, Kivelä S L. Prognosis of diastolic and systolic orthostatic hypotension in older persons. Arch Intern Med. 1999;159(03):273–280. [PubMed] [Google Scholar]

6. Balcıoğlu A S, Müderrisoğlu H. Diabetes and cardiac autonomic neuropathy: clinical manifestations, cardiovascular consequences, diagnosis and treatment. World J Diabetes. 2015;6(01):80–91. [PMC free article] [PubMed] [Google Scholar]

7. Fleg J L, Evans G W, Margolis K L et al. Orthostatic hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial: prevalence, incidence, and prognostic significance. Hypertension. 2016;68(04):888–895. [PMC free article] [PubMed] [Google Scholar]

8. Ziegler D. Cardiovascular autonomic Neuropathy: clinical manifestations and measurement. Diabetes Rev (Alex) 1999;7:342–357. [Google Scholar]

9. Ziegler D, Schatz H, Conrad F, Gries F A, Ulrich H, Reichel G. Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Diabetes Care. 1997;20(03):369–373. [PubMed] [Google Scholar]

10. Karavaev A S, Ishbulatov Y M, Ponomarenko V I et al. Model of human cardiovascular system with a loop of autonomic regulation of the mean arterial pressure. J Am Soc Hypertens. 2016;10(03):235–243. [PubMed] [Google Scholar]

11. Ziegler D, Gries F A. Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Diabetes. 1997;46 02:S62–S66. [PubMed] [Google Scholar]

12. Prendergast J J.Diabetic autonomic neuropathy: Part 2. TreatmentPractical Diabetology, June 2001; 30–36

13. Ziegler D, Ametov A, Barinov A et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006;29(11):2365–2370. [PubMed] [Google Scholar]

14. Ametov A S, Barinov A, Dyck P J et al. The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care. 2003;26(03):770–776. [PubMed] [Google Scholar]

15. Ziegler D, Low P A, Litchy W J et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(09):2054–2060. [PMC free article] [PubMed] [Google Scholar]

16. Jones P K, Shaw B H, Raj S R. Orthostatic hypotension: managing a difficult problem. Expert Rev Cardiovasc Ther. 2015;13(11):1263–1276. [PMC free article] [PubMed] [Google Scholar]

17. Eschlböck S, Wenning G, Fanciulli A. Evidence-based treatment of neurogenic orthostatic hypotension and related symptoms. J Neural Transm (Vienna) 2017;124(12):1567–1605. [PMC free article] [PubMed] [Google Scholar]

18. Gomes M B, Negrato C A. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr. 2014;6(01):80–96. [PMC free article] [PubMed] [Google Scholar]

19. Freeman R, Abuzinadah A R, Gibbons C, Jones P, Miglis M G, Sinn D I. Orthostatic hypotension. J Am Coll Cardiol. 2018;72(11):1294–1309. [PubMed] [Google Scholar]

20. Zhang H, Jia H, Liu Jet al. Combined R-alpha-lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease J Cell Mol Med 201014(1-2):215–225. [PMC free article] [PubMed] [Google Scholar]

21. Biosa A, Outeiro T F, Bubacco L, Bisaglia M. Diabetes mellitus as a risk factor for Parkinson's disease: a molecular point of view. Mol Neurobiol. 2018;55(11):8754–8763. [PubMed] [Google Scholar]

22. Aysin B, Colombo J, Aysin E.Comparison of HRV analysis methods during orthostatic challenge: HRV with respiration or without?29thInt Conf IEEE EMBS Lyon, France, 2007 [PubMed]

23. Akselrod S, Gordon D, Ubel F A, Shannon D C, Berger A C, Cohen R J.Power spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat cardiovascular control Science 1981213(4504):220–222. [PubMed] [Google Scholar]

24. Akselrod S, Gordon D, Madwed J B, Snidman N C, Shannon D C, Cohen R J.Hemodynamic regulation: investigation by spectral analysis Am J Physiol 1985249(4 Pt 2):H867–H875. [PubMed] [Google Scholar]

25. Akselrod S, Eliash S, Oz O, Cohen S.Hemodynamic regulation in SHR: investigation by spectral analysis Am J Physiol 1987253(1 Pt 2):H176–H183. [PubMed] [Google Scholar]

26. Akselrod S. Spectral analysis of fluctuations in cardiovascular parameters: a quantitative tool for the investigation of autonomic control. Trends Pharmacol Sci. 1988;9(01):6–9. [PubMed] [Google Scholar]

27. Colombo J, Arora R R, DePace N L, Vinik A I. New York, NY: Springer Science + Business Media; 2014. Clinical Autonomic Dysfunction: Measurement, Indications, Therapies, and Outcomes. [Google Scholar]

28. Lee W J, Kim S W, Kim G H et al. Alpha-lipoic acid activates dimethylarginine dimethylaminohydrolase in cultured endothelial cells. Biochem Biophys Res Commun. 2010;398(04):653–658. [PubMed] [Google Scholar]

29. Gouty S, Regalia J, Cai F, Helke C J.Alpha-lipoic acid treatment prevents the diabetes-induced attenuation of the afferent limb of the baroreceptor reflex in rats Auton Neurosci 2003108(1-2):32–44. [PubMed] [Google Scholar]

30. Queiroz T M, Guimarães D D, Mendes-Junior L G, Braga V A. α-lipoic acid reduces hypertension and increases baroreflex sensitivity in renovascular hypertensive rats. Molecules. 2012;17(11):13357–13367. [PMC free article] [PubMed] [Google Scholar]

31. Mohammadi V, Khorvash F, Feizi A, Askari G. Does alpha-lipoic acid supplementation modulate cardiovascular risk factors in patients with stroke? A randomized, double-blind clinical trial. Int J Prev Med. 2018;9:34. [PMC free article] [PubMed] [Google Scholar]

32. Tardif J C, Rhéaume E. Lipoic acid supplementation and endothelial function. Br J Pharmacol. 2008;153(08):1587–1588. [PMC free article] [PubMed] [Google Scholar]

33. Bangalore S, Messerli F H, Wun C C et al. J-curve revisited: an analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) Trial. Eur Heart J. 2010;31(23):2897–2908. [PubMed] [Google Scholar]

34. Mohammadi V, Dehghani S, Askari G. Does alpha-lipoic acid supplement regulate blood pressure?A systematic review of randomized, double-blind placebo-controlled clinical trials. Int J Prev Med. 2017;8:33–38. [PMC free article] [PubMed] [Google Scholar]

Articles from The International Journal of Angiology : Official Publication of the International College of Angiology, Inc are provided here courtesy of Thieme Medical Publishers

(r)Alpha Lipoic Acid Is a Safe, Effective Pharmacologic Therapy of Chronic Orthostatic Hypotension Associated with Low Sympathetic Tone (2024)

References

Top Articles
Latest Posts
Recommended Articles
Article information

Author: Gov. Deandrea McKenzie

Last Updated:

Views: 6448

Rating: 4.6 / 5 (66 voted)

Reviews: 89% of readers found this page helpful

Author information

Name: Gov. Deandrea McKenzie

Birthday: 2001-01-17

Address: Suite 769 2454 Marsha Coves, Debbieton, MS 95002

Phone: +813077629322

Job: Real-Estate Executive

Hobby: Archery, Metal detecting, Kitesurfing, Genealogy, Kitesurfing, Calligraphy, Roller skating

Introduction: My name is Gov. Deandrea McKenzie, I am a spotless, clean, glamorous, sparkling, adventurous, nice, brainy person who loves writing and wants to share my knowledge and understanding with you.