Can I Take Alpha-Lipoic Acid with Viagra (Sildenafil)?

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Does Alpha-Lipoic Acid Interact With Viagra?

Viagra is a prescription PDE5 inhibitor for erectile dysfunction, usually 50 mg taken about an hour before sex, adjustable to 25 or 100 mg, no more than once a day [1]. ALA is a sulfur-containing antioxidant the body also makes as a cofactor for mitochondrial enzymes, sold over the counter as a dietary supplement; a Drugs@FDA search for lipoic acid and thioctic acid returns no approved drug application [5][6].

ALA is not named in the Viagra interaction section, but that does not establish that the combination is safe or that an interaction cannot occur [1]. No study of ALA taken with sildenafil was found, so any effect of ALA on sildenafil blood levels, and any spacing interval between them, is unknown.

For comparison, here is what the label does treat as significant. Organic nitrates and nitrites in any form are contraindicated [1]. The label describes additive blood-pressure lowering with alpha-blockers and says Viagra should be started at 25 mg once alpha-blocker therapy is stable [1]. Amlodipine 5 or 10 mg plus sildenafil 100 mg added a mean 8/7 mmHg fall in supine blood pressure in hypertensive patients [1]. Ritonavir raised sildenafil exposure (AUC) 11-fold, erythromycin raised peak concentration 160% and AUC 182%, and saquinavir raised them 140% and 210% [1]. Alcohol at a mean peak of 0.08% did not worsen alcohol's blood-pressure effect [1].

Sildenafil is cleared mainly by CYP3A4, with CYP2C9 a minor route [1].

Blood Pressure: What Each One Does on Its Own

Sildenafil enhances the nitric oxide/cGMP response involved in erection, and the label also describes systemic vasodilatory properties [1]. A single 100 mg dose lowered supine blood pressure in healthy volunteers by a mean maximum of about 8.4/5.5 mmHg, with no dose relationship between 25 and 100 mg [1]. The label advises caution when sildenafil is combined with antihypertensives or alpha-blockers because the effect can lead to hypotension [1].

ALA's effect has been pooled: 11 randomized trials covering 674 adults found systolic blood pressure 5.46 mmHg lower (95% CI -9.27 to -1.65) and diastolic 3.36 mmHg lower (95% CI -4.99 to -1.74) on ALA than on control, with significant effects at doses under 800 mg/day and durations of 12 weeks or less [2].

Blood Sugar: ALA's Real Effect and Its Rare Complication

ALA is not a neutral supplement for glucose. A meta-analysis of 41 articles found fasting glucose WMD -6.57 (95% CI -11.91 to -1.23) and HbA1c WMD -0.35 (95% CI -0.55 to -0.15), with no change in insulin or HOMA-IR [3]. A dose-response meta-analysis of 16 trials in 1,035 people with type 2 diabetes found HbA1c 0.32 percentage points lower per 500 mg/day, on a J-shaped curve, and the authors judged all the effects below clinically important thresholds [7]. In a 4-week placebo-controlled trial of 74 people with type 2 diabetes, oral ALA at 600, 1,200 or 1,800 mg/day raised insulin-stimulated glucose disposal by 27% versus placebo, with no difference between doses [8].

Separately, ALA belongs to the sulfhydryl compounds linked to insulin autoimmune syndrome (Hirata disease), a rare cause of spontaneous low blood sugar with very high insulin levels and insulin autoantibodies in people who never took insulin [4]. Six Caucasian patients, median age 63, taking 600 mg/day developed fasting and after-meal hypoglycemia 30 to 120 days after starting it; five carried HLA-DRB1*04:03 [4]. Cases have also been reported in a 67-year-old woman with type 2 diabetes whose hypoglycemia began two weeks after starting ALA [9], a 35-year-old woman from Sri Lanka [10], and an Indian man with insulin above 1,000 microIU/mL [11]. In Caucasians the syndrome is less than one-fifth as common as in Japan but is increasingly recognized, and knowing a patient takes ALA can prevent a mistaken search for an insulinoma [12].

The Viagra label lists "hypoglycemic reaction" among events reported in fewer than 2% of patients in controlled trials, but says a causal relationship to Viagra is uncertain [1].

Doses Used in Studies, and the Overdose Signal

These are study doses, not recommended doses: 600 mg/day in the reported autoimmune hypoglycemia cases [4]; 600, 1,200 or 1,800 mg/day orally for 4 weeks in the type 2 diabetes trial [8]; and 600 mg intravenously daily for 3 weeks in the neuropathy trials [13]. Oral ALA is about 30% bioavailable with a short half-life [5].

Large single ingestions are a separate danger. A 42-year-old woman who took 6 g (ten 600 mg tablets, 92.3 mg/kg) had refractory seizures, metabolic acidosis, kidney injury and multi-organ failure and died; the report counted nine published ALA toxicity cases, including a 14-year-old who died after 6 g [14].

Timing, and What the Viagra Label Flags

On its own, sildenafil peaks 30 to 120 minutes after a fasting oral dose (median 60 minutes), a high-fat meal delays that peak by about 60 minutes and cuts peak concentration by 29%, and its terminal half-life is about 4 hours [1].

The Viagra label identifies sudden vision loss in one or both eyes (which can be non-arteritic anterior ischemic optic neuropathy) and sudden hearing loss, sometimes with tinnitus and dizziness, as warning signs requiring prompt medical attention [1]. It also says an erection lasting more than 4 hours needs immediate medical assistance, noting that untreated priapism can cause permanent loss of potency [1]. It states that sexual activity carries cardiac risk in men with heart disease, and that nitrates remain contraindicated with no established safe interval after a dose [1].

Viagra is a prescription oral tablet available in 25 mg, 50 mg, and 100 mg strengths [15].